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Hematology - Hematopoietic Stem-Cell Transplantation (HSCT) and Related Complications - Fast Facts | NEJM Resident 360

HSCT is often the only treatment providing a chance of cure in refractory hematological malignancies and some bone-marrow disorders. The two types of HSCT are allogeneic (from a donor) and autologous (from the patient). 

Autologous Transplantation

Autologous transplantation can be thought of as high-dose chemotherapy with stem-cell rescue. First, the patient’s own stem cells are collected and stored, then a myeloablative chemotherapy regimen (described below) is administered, followed by the return of the patient’s own stem cells. The goal is for the high-dose chemotherapy regimen to kill any remaining malignant cells and allow the patient’s own stem cells to reconstitute the bone marrow. Matching for human leukocyte antigens (HLAs) is not necessary.

Allogeneic Transplantation

Matching for HLAs is performed to find a desirable donor. Potential stem-cell donor sources include siblings, matched unrelated donors, umbilical cord blood, and haploidentical donors. Stem cells can be collected from the peripheral blood or bone marrow and reintroduced into the recipient intravenously. The stem cells home in on the marrow and regenerate hematopoiesis. Engraftment can take 2 to 4 weeks, depending on the donor type.

Preparative conditioning regimen (chemotherapy with or without irradiation): The transplantation procedure involves one of the following preparative regimens with the goal of consolidating treatment of the underlying disease and suppressing the recipient immune system to prevent graft rejection. The choice of preparative regimen depends on patient age and comorbidities:

• Myeloablative regimen is expected to destroy the hematopoietic cells in the bone marrow to result in profound pancytopenia. The resultant pancytopenia is often fatal unless restored by stem-cell infusion. Myeloablative regimens are usually reserved for younger, otherwise healthy patients.

• Nonmyeloablative regimens cause minimal cytopenias. The regimen prevents host defenses from rejecting the donor cells.

• Reduced-intensity regimens are intermediate regimens that may cause prolonged cytopenias and require stem-cell support.

Complications: Persistent cytopenias beyond 3 to 4 weeks suggest graft failure. Graft-versus-host disease (GVHD) is unique to allogeneic transplantation.

Important Complications of HSCT and Their Timeline

(Source: Harrison’s Principles of Internal Medicine, 18th Edition. Reproduced with permission from McGraw-Hill Education, Inc.)

Acute GVHD can present as a maculopapular rash, liver dysfunction, and/or diarrhea, because the main targets of the attack are the skin, liver, and gastrointestinal (GI) tract.

• Acute GVHD remains the major cause of morbidity and mortality, especially in unrelated allogeneic transplantation.

• Early recognition and prompt treatment are essential. Immunosuppressive agents such as methotrexate, sirolimus, cyclosporine, and tacrolimus are used for prevention, and glucocorticoids, ruxolitinib, and other immunosuppressive agents are used for treatment.

Chronic GVHD can present with rash or sclerodermatous skin changes; sicca syndrome; obliterative bronchiolitis; liver dysfunction, including cholestasis and bile duct degeneration; diarrhea or upper GI symptoms; and joint, muscle, or fascia tightness. Most patients undergoing allogeneic HSCT will develop some form of chronic GVHD. Chronic GVHD is associated with reduced risk of relapse (both the graft-versus-leukemia effect and GVHD are recognized as alloantigens), and treatment involves immunosuppressive agents. These patients are at high risk for infection.

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